Dynamically detuned oscillations account for the coupled rate and temporal code of place cell firing

Firing of place cells in the exploring rat conveys doubly coded spatial information: both the rate of spikes and their timing relative to the phase of the ongoing field theta oscillation are correlated with the location of the animal. Specifically, the firing rate of a place cell waxes and wanes, while the timing of spikes precesses monotonically as the animal traverses the portion of the environment preferred by the cell. We propose a mechanism for the generation of this firing pattern that can be applied for place cells in all three hippocampal subfields and that encodes spatial information in the output of the cell without relying on topographical connections or topographical input. A single pyramidal cell was modeled so that the cell received rhythmic inhibition in phase with theta field potential oscillation on the soma and was excited on the dendrite with input depending on the speed of the rat. The dendrite sustained an intrinsic membrane potential oscillation, frequency modulated by its input. Firing probability of the cell was determined jointly by somatic and dendritic oscillations. Results were obtained on different levels of abstraction: a purely analytical derivation was arrived at, corroborated by numerical simulations of rate neurons, and an extension of these simulations to spiking neurons was also performed. Realistic patterns of rate and temporal coding emerged and were found to be inseparable. These results may have implications on the robustness of information coding in place cell firing and on the ways information is processed in structures downstream to the hippocampus.     

Use of PET to monitor the response of lung cancer to radiation treatment

Approximately 170,000 people are diagnosed with lung cancer in the United States each year. Many of these patients receive external beam radiation for treatment. Fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is increasingly being used in evaluating non-small cell lung cancer and may be of clinical utility in assessing response to treatment. In this report, we present FDG PET images and data from two patients who were followed with a total of eight and seven serial FDG PET scans, respectively, through the entire course of their radiation therapy. Changes in several potential response parameters are shown versus time, including lesion volume (V(FDG)) by PET, SUVav, SUVmax, and total lesion glycolysis (TLG) during the course of radiotherapy. The response parameters for patient 1 demonstrated a progressive decrease; however, the response parameters for patient 2 showed an initial decrease followed by an increase. The data presented here may suggest that the outcome of radiation therapy can be predicted by PET imaging, but this observation requires a study of additional patients.     

Intensity of 18fluorodeoxyglucose uptake in positron emission tomography distinguishes between indolent and aggressive non-Hodgkin's lymphoma.

PURPOSE: (18)Fluorodeoxyglucose positron emission tomography (FDG PET) is widely used for the staging of lymphoma. We investigated whether the intensity of tumor FDG uptake could differentiate between indolent and aggressive disease. MATERIALS AND METHODS: PET studies of 97 patients with non-Hodgkin's lymphoma who were untreated or had relapsed and/or persistent disease and had not received treatment within the last 6 months were analyzed, and the highest standardized uptake value (SUV) per study was recorded. Correlations were made with histopathology. RESULTS: FDG uptake was lower in indolent than in aggressive lymphoma for patients with new (SUV, 7.0 +/- 3.1 v 19.6 +/- 9.3; P < .01) and relapsed (SUV, 6.3 +/- 2.7 v 18.1 +/- 10.9; P = .04) disease. Despite overlap between indolent and aggressive disease in the low SUV range (indolent, 2.3 to 13.0; aggressive, 3.2 to 43.0), all cases of indolent lymphoma had an SUV 10 excluded indolent lymphoma with a specificity of 81%. With a higher cutoff for the SUV, the specificity would have been higher. CONCLUSION: FDG uptake is lower in indolent than in aggressive lymphoma. Patients with NHL and SUV > 10 have a high likelihood for aggressive disease. This information may be helpful if there is discordance between biopsy and clinical behavior.     

Effects of pregabalin on spinal fusion

European Spine Journal - Gamma-aminobutyric acid analogues are commonly used to treat neuropathic and chronic pain before and after spinal surgery in recent years. Aim of this study is to...     

Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila

Autophagy, a cellular process of cytoplasmic degradation and recycling, is induced in Drosophila larval tissues during metamorphosis, potentially contributing to their destruction or reorganization. Unexpectedly, we find that flies lacking the core autophagy regulator Atg7 are viable, despite severe defects in autophagy. Although metamorphic cell death is perturbed in Atg7 mutants, the larval-adult midgut transition proceeds normally, with extended pupal development compensating for reduced autophagy. Atg7-/- adults are short-lived, hypersensitive to nutrient and oxidative stress, and accumulate ubiquitin-positive aggregates in degenerating neurons. Thus, normal levels of autophagy are crucial for stress survival and continuous cellular renewal, but not metamorphosis.     

Phase and amplitude binning for 4D-CT imaging

We compare the consistency and accuracy of two image binning approaches used in 4D-CT imaging. One approach, phase binning (PB), assigns each breathing cycle 2pi rad, within which the images are grouped. In amplitude binning (AB), the images are assigned bins according to the breathing signal's full amplitude. To quantitate both approaches we used a NEMA NU2-2001 IEC phantom oscillating in the axial direction and at random frequencies and amplitudes, approximately simulating a patient's breathing. 4D-CT images were obtained using a four-slice GE Lightspeed CT scanner operating in cine mode. We define consistency error as a measure of ability to correctly bin over repeated cycles in the same field of view. Average consistency error mue+/-sigmae in PB ranged from 18%+/-20% to 30%+/-35%, while in AB the error ranged from 11%+/-14% to 20%+/-24%. In PB nearly all bins contained sphere slices. AB was more accurate, revealing empty bins where no sphere slices existed. As a proof of principle, we present examples of two non-small cell lung carcinoma patients' 4D-CT lung images binned by both approaches. While AB can lead to gaps in the coronal images, depending on the patient's breathing pattern, PB exhibits no gaps but suffers visible artifacts due to misbinning, yielding images that cover a relatively large amplitude range. AB was more consistent, though often resulted in gaps when no data existed due to patients' breathing pattern. We conclude AB is more accurate than PB. This has important consequences to treatment planning and diagnosis.     

Changes in FDG Tumor Uptake during and after Fractionated Radiation Therapy in a Rodent Tumor Xenograft

OBJECTIVE: The uptake of FDG was measured before, during, and after fractionated radiation in order to evaluate the potential of FDG-PET imaging as an indicator of tumor response.METHODS: The study was performed with nude rats bearing the human neuroblastoma BE(2)C tumor xenografts. Tumors were irradiated with 10 fractions of 2 Gy using a 320 kV(p) X-ray unit. Following a baseline FDG-PET scan, repeat scans were performed weekly until animal sacrifice. The rodents were given up to 10 FDG-PET scans, over a period of up to 75 days posttreatment.RESULTS AND CONCLUSIONS: Neither, the average and maximum activity/cc of FDG tumor uptake, nor the respective standardized uptake values (SUV), correlated with tumor response. Instead, the total FDG uptake (defined as the product of the average FDG activity/cc with the tumor volume) correlated better with tumor response.     

Use of PET to monitor the response of lung cancer to radiation treatment

Approximately 170,000 people arediagnosed with lung cancer in the United States each year. Manyof these patients receive external beam radiation for treatment. Fluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) is increasingly being used in evaluating non-small cell lung cancer and may be of clinical utility in assessing response to treatment. In this report, we present FDG PET images and data from two patients who were followed with a total of eight and seven serial FDG PET scans, respectively, through the entire course of their radiation therapy. Changes in several potential response parameters are shown versus time, including lesion volume (V_FDG) by PET, SUV_av, SUV_max, and total lesion glycolysis (TLG) during the course of radiotherapy. The response parameters for patient 1 demonstrated a progressive decrease; however, the response parameters for patient 2 showed an initial decrease followed by an increase. The data presented here may suggest that the outcome of radiation therapy can be predicted by PET imaging, but this observation requires a study of additional patients. Received 20 January and in revised form 29 February 2000     

三氧化二砷对人胃癌裸鼠移植瘤Flt-1、KDR和VEGFR-3表达的影响

目的:探讨As2O3对人胃癌移植瘤细胞Flt-1、KDR和VEGFR-3表达的影响,揭示As2O3在肿瘤血管及淋巴道形成和转移中的作用。方法:建立人胃癌裸鼠移植瘤模型,分组给予2.5mg/kg和5mg/kg的As2O3治疗;用免疫荧光-激光共聚焦技术检测肿瘤组织Flt-1、KDR的表达;用免疫组化方法检测VEGFR-3表达,并采用图像信号采集与分析系统进行图像扫描分析。结果:治疗组Flt-1、KDR和VEGFR-3的表达均较对照组明显减弱;高剂量组Flt-1、KDR和VEGFR-3的表达明显弱于低剂量组者。图像灰度统计分析显示差异具有显著性意义。结论:As2O3对人胃癌移植瘤细胞Flt-1、KDR及VEGFR-3表达均有抑制作用,提示As2O3可能通过抑制VEGF受体家族Flt-1、KDR及VEGFR-3表达抑制肿瘤血管及淋巴管的生成。     

Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET).

PURPOSE: Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as part of their treatment. Three-dimensional conformal radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately delineate the target lesion and normal tissues. Clinical studies, however, indicate that positron emission tomography (PET) has higher sensitivity than CT in detecting and staging of mediastinal metastases. Imaging with fluoro-2-deoxyglucose (FDG) PET in conjunction with CT, therefore, can improve the accuracy of lesion definition. In this pilot study, we investigated the potential benefits of incorporating PET data into the conventional treatment planning of NSCLC. Case-by-case, we prospectively analyzed planning target volume (PTV) and lung toxicity changes for a cohort of patients. MATERIALS AND METHODS: We have included 11 patients in this study. They were immobilized in the treatment position and CT simulation was performed. Following CT simulation, PET scanning was performed in the treatment position using the same body cast that was produced for CT simulation and treatment. The PTV, along with the gross target volume (GTV) and normal organs, was first delineated using the CT data set. The CT and PET transmission images were then registered in the treatment planning system using either manual or automated methods, leading to consequent registration of the CT and emission images. The PTV was then modified using the registered PET emission images. The modified PTV is seen simultaneously on both CT and PET images, allowing the physician to define the PTV utilizing the information from both data sets. Dose-volume histograms (DVHs) for lesion and normal organs were generated using both CT-based and PET+CT-based treatment plans. RESULTS: For all patients, there was a change in PTV outline based on CT images versus CT/PET fused images. In seven out of 11 cases, we found an increase in PTV volume (average increase of 19%) to incorporate distant nodal disease. Among these patients, the highest normal-tissue complication probability (NTCP) for lung was 22% with combined PET/CT plan and 21% with CT-only plan. In other four patients PTV was decreased an average of 18%. The reduction of PTV in two of these patients was due to excluding atelectasis and trimming the target volume to avoid delivering higher radiation doses to nearby spinal cord or heart. CONCLUSIONS: The incorporation of PET data improves definition of the primary lesion by including positive lymph nodes into the PTV. Thus, the PET data reduces the likelihood of geographic misses and hopefully improves the chance of achieving local control.